Reversible pulmonary arterial hypertension as a complication of dasatinib treatment, with effi cacious and safe continuation of chronic myeloid leukaemia therapy with nilotinib

Abstract

Tyrosine kinase inhibitors, such as dasatinib, are used in the treatment of chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) associated with the Philadelphia chromosome.
Recently however, dasatinib-related pulmonary arterial hypertension (PAH) has been described, which is a rarely arising side effect, and in most cases reversible after discontinuating the dasatnib therapy. A case study is presented of a 39-year-old woman in whom CML was diagnosed in 2005. Therapy had been started with hydroxyurea and continued for 4 months, followed by treatment with imatinib that continued on for 60 months. Due to resistance, imatinib was then
replaced by dasatinib. Following 3 years treatment, the patient presented with dyspnoea after performing physical effort, where lymphocyte-predominant pleural effusions together with pulmonary
artery hypertension were detected. When secondary causes of PAH had been excluded, a diagnosis of dasatinib-related PAH was made. The dasatinib was therefore discontinued and the patient received
nilotinib therapy for treating CML and sildenafi l therapy for the PAH. The latter treatment was however halted after 1.5 years, as by then the PAH symptoms had been resolved; this having been confi rmed after 4 weeks, where normal pulmonary artery pressure (PAP) was observed during rest and on exertion following heart catheterization. A major molecular response of the CML was thus achieved using the nilotinib treatment without increasing PAP.